Remarkable Alteration of PD-L1 Expression after Immune Checkpoint Therapy in Patients with Non-Small-Cell Lung Cancer: Two Autopsy Case Reports

Pembrolizumab is an immune checkpoint inhibitor (ICI), currently recommended as thefirst-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) showing 50% expression of programmed death-ligand 1 (PD-L1). Previously it was reported that platinum-based chemotherapy may change PD-L1 expression in solid cancers. However, no reports addressing alteration of PD-L1 expression after ICI therapy in NSCLC are available so far. The patients wereJapanesemales 83 and 87 years old,whowere diagnosedwithNSCLC based on the transbronchial lung biopsies showing sarcomatoid feature with high PD-L1 expression. They received Pembrolizumab,however, passed awaywith disease progression on day 27 and day 9, respectively. PD-L1, PD1, andCD8 antibodies were applied to pretreatment tumor biopsies and autopsy specimens. Immunoexpression of all themarkers was evaluated using Aperio ImageScope. We found that PD-L1 expression decreased significantly from 75.6% to 13.2% and from 100% to 58.8%, in patients 1 and 2, respectively. This alteration was less prominent in the perinecrotic tumor area. A considerable decrease of PD-L1 score was linked with a little effect of Pembrolizumab in our patients. This association might be one of the contributing mechanisms of resistance to ICI and needs further investigation in large-scale studies